Updates in characteristics and survival rates of cirrhosis in a nationwide cohort of real-world U.S. patients, 2003-2021.

BACKGROUND: Adverse outcomes of cirrhosis remain a top priority. AIMS: We examined the distribution of cirrhosis causes, HCC incidence and mortality and related changes over time in a nationwide U.S. METHODS: A retrospective study of a national sample of commercially insured patients with cirrhosis from Optum's de-identified Clinformatics® Data Mart Database (CDM). RESULTS: A total of 628,743 cirrhosis cases were identified with 45% having NAFLD, 19.5% HCV, and 16.3% ALD. African Americans had the highest rate of decompensation (60.6%), while Asians had the highest rate of HCC (2.4%), both p < 0.001. African Americans more frequently had HCV (28.4%) while Hispanic/Latinos more frequently had NAFLD (49.2%, p < 0.001). Patients in the 2014-2021 cohort were significantly older (63.0 ± 12.8 vs. 57.0 ± 14.3), less frequently decompensated (54.5% vs. 58.3%) but more frequently had HCC (1.7% vs. 0.6%) and NAFLD (46.5% vs. 44.2%), all p < 0.001. The overall annual incidence of HCC was 0.76% (95% CI: 0.75-0.77) with a 5-year cumulative incidence of 4.03% (95% CI: 3.98-4.09), with significant variation by sex, race/ethnicity, and cirrhosis aetiology. The overall median years of survival were 11.4 (95% CI: 11.3-11.5) with a 5-year cumulative survival of 73.4% (95% CI: 73.3%-73.6%), also with significant disparities in similar subgroups (lowest in cryptogenic cirrhosis and worse in 2014-2021 vs. 2003-2013). The 2014-2021 period was independently associated with worse survival (aHR: 1.14, 95% CI: 1.08-1.20). CONCLUSIONS: HCC incidence and survival vary by aetiology among patients with cirrhosis, with cryptogenic cirrhosis having the lowest survival and lower survival in the more recent time period.

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis.

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.

Mortality in patients with chronic hepatitis B treated with tenofovir or entecavir: A multinational study.

BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Upper limit of normal ALT levels in health and metabolic diseases: Pooled analysis of 423,355 individuals with bootstrap modelling.

INTRODUCTION: Given the global rise in obesity-related metabolic diseases, the upper limit of normal (ULN) alanine aminotransferase (ALT) in individuals with and without metabolic diseases may have changed. We performed a meta-analysis combined with bootstrap modelling to estimate the ALT ULN levels for individuals with and without metabolic diseases. METHODS AND RESULTS: Two separate searches of the PubMed, Embase and Cochrane databases were performed, one to identify healthy individuals which yielded 12 articles (349,367 individuals); another to include those with potential metabolic diseases but without known liver disease which yielded 35 articles (232,388 individuals). We estimated the mean ALT using a random-effects mixed model and the ULN level (95th-percentile value) via a bootstrap model with 10,000 resamples. In individuals without metabolic diseases and known liver disease, the ALT ULN levels were 32 U/L overall; 36 U/L in males and 28 U/L in females. In analyses that included individuals with metabolic diseases, the ALT ULN levels were 40 U/L among the overweight/obese (29 U/L if normal weight) and 36 U/L among those with type 2 diabetes mellitus (T2DM) (33 U/L if no T2DM). On meta-regression of study-level factors, body mass index (coefficient 1.49, 95% CI 0.11-2.86, p = 0.03), high-density lipoprotein (coefficient -0.47, 95% CI -0.85-(-0.08), p = 0.02) and triglycerides (coefficient 0.19, 95% CI 0.12-0.25, p < 0.0001) correlated with ALT. CONCLUSION: We provide expected ranges of ALT ULN levels for individuals without known liver disease without metabolic diseases and those with or without T2DM and/or are normal weight or overweight/obese. These data may have implications for clinical care and screening.

Antiviral Therapy Utilization and 10-Year Outcomes in Resected Hepatitis B Virus- and Hepatitis C Virus-Related Hepatocellular Carcinoma.

PURPOSE: There are limited data on antiviral treatment utilization and its impact on long-term outcomes of hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after hepatic resection. We aimed to determine the utilization and impact of antivirals in HBV- and HCV-related HCC. METHODS: This cohort study included 1,906 participants (1,054 HBV-related HCC and 852 HCV-related HCC) from 12 international sites. All participants had HBV- or HCV-related HCC and underwent curative surgical resection. The primary outcome was the utilization of antiviral therapy, and the secondary outcome was long-term overall survival (OS). RESULTS: The mean (±standard deviation [SD]) age was 62.1 (±11.3) years, 74% were male, and 84% were Asian. A total of 47% of the total cohort received antiviral therapy during a mean (±SD) follow-up of 5.0 (±4.3) years. The overall antiviral utilization for participants with HBV-related HCC was 57% and declined over time, from 65% before 2010, to 60% from 2010 to 2015, to 47% beyond 2015, P < .0001. The overall utilization of antivirals for HCV-related HCC was 35% and increased over time, from 24% before 2015 to 74% from 2015 and beyond, P < .0001. The 10-year OS was lower in untreated participants for both HBV (58% v 61%) and HCV participants (38% v 82%; both P < .0001). On multivariable Cox regression analysis adjusted for relevant confounders, antiviral therapy initiated before or within 6 months of HCC diagnosis was independently associated with lower mortality in both HBV- (adjusted hazard ratio [aHR], 0.60 [95% CI, 0.43 to 0.83]; P = .002) and HCV-related HCC (aHR, 0.18 [95% CI, 0.11 to 0.31]; P < .0001). CONCLUSION: Antiviral therapy is associated with long-term survival in people with HBV- or HCV-related HCC who undergo curative resection but is severely underutilized.

Racial and ethnic disparities in untreated patients with hepatitis C virus-related hepatocellular carcinoma but not in those with sustained virologic response.

BACKGROUND: Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival. AIM: To evaluate the impact of HCV treatment on such disparities. METHODS: In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia. RESULTS: The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001). CONCLUSION: DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

Global incidence of adverse clinical events in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. METHODS: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. RESULTS: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). CONCLUSION: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Incidence and predictors of hepatocellular carcinoma in NAFLD without diagnosed cirrhosis: a nationwide real-world U.S. study.

BACKGROUND: A substantial proportion of patients with nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) do not have cirrhosis. Data regarding the incidence and predictors of HCC development in NAFLD without cirrhosis are limited. We conducted a large, national study of NAFLD patients without documented cirrhosis to examine the incidence and predictors for HCC development. METHODS: This retrospective study included 751,603 NAFLD patients (54% female) without documented cirrhosis derived from the deidentified Optum Clinformatics® Data Mart Database. Patients with cirrhosis, platelets < 120,000/µL or FIB-4 values > 2.67 were excluded. RESULTS: The mean age was 53.7 ± 15.0 years, 45.9% were male, 39.5% had diabetes, 57.6% were White, 18.4% Hispanic, 8.2% Black and 4.9% were Asian. The mean platelet count was 264,000 ± 72,000/µL, and 96.3% of patients had a FIB-4 < 1.30. Over 1,686,607 person-years of follow-up, there were 76 incident cases of HCC, resulting in an HCC incidence rate of 0.05 per 1000 person-years. There was a higher HCC incidence rate among patients with platelets ≤ 150,000/µL, versus those with platelets > 150,000/µL (0.23 per 1000 person-years, vs. 0.04 per 1000 person-years, p = 0.02) but not in subgroup analyses for age, sex, race/ethnicity or diabetes. Using multivariable Cox proportional hazards model adjusted multiple confounders, platelet count ≤ 150,000/µL remained an independent predictor of HCC development (adjusted HR 5.80, 95% CI 1.67-20.1, p = 0.006). CONCLUSION: HCC incidence in NAFLD without documented cirrhosis was below the threshold for cost-effective HCC surveillance in overall and multiple subgroup analyses. Platelet count < 150,000/µL may be a useful predictor of HCC development in this population.

Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation.

BACKGROUND/AIMS: Finite nucleos(t)ide analog (NA) therapy has been proposed as an alternative treatment strategy for chronic hepatitis B (CHB), but biomarkers for post-treatment monitoring are limited. We investigated whether measuring hepatitis B core-related antigen (HBcrAg) after NA cessation may stratify the risk of subsequent clinical relapse (CR). METHODS: This retrospective multicenter analysis enrolled adults with CHB who were prospectively monitored after discontinuing entecavir or tenofovir with negative HBeAg and undetectable HBV DNA at the end of treatment (EOT). Patients with cirrhosis or malignancy were excluded. CR was defined as serum alanine aminotransferase > two times the upper limit of normal with recurrent viremia. We applied time-dependent Cox proportional hazard models to clarify the association between HBcrAg levels and subsequent CR. RESULTS: The cohort included 203 patients (median age, 49.8 years; 76.8% male; 60.6% entecavir) who had been treated for a median of 36.9 months (interquartile range [IQR], 36.5-40.1). During a median post-treatment follow-up of 31.7 months (IQR, 16.7-67.1), CR occurred in 104 patients with a 5-year cumulative incidence of 54.8% (95% confidence interval [CI], 47.1-62.4%). Time-varying HBcrAg level was a significant risk factor for subsequent CR (adjusted hazard ratio [aHR], 1.53 per log U/mL; 95% CI, 1.12-2.08) with adjustment for EOT HBsAg, EOT anti-HBe, EOT HBcrAg and time-varying HBsAg. During follow-up, HBcrAg <1,000 U/mL predicted a lower risk of CR (aHR, 0.41; 95% CI, 0.21-0.81). CONCLUSION: Dynamic measurement of HBcrAg after NA cessation is predictive of subsequent CR and may be useful to guide post-treatment monitoring.

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Pretreatment gamma-glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs.

Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)-related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liver-related, and non-liver-related mortality. The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 person-years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month-6-GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92-3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003-1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994-0.998, p = 0.001), and age (HR/CI: 1.06/1.04-1.07, p < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79-6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004-1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990-0.997, p = 0.001), age (HR/CI: 1.03/1.01-1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15-0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000-1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25-75, and >75 percentile of pretreatment GGT levels was observed with respect to the all-cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.

Use and Outcomes of Hepatitis B Virus-positive Grafts for Kidney or Heart Transplantation in the United States From 1999 to 2021.

BACKGROUND: The gap between demand and supply for solid organ transplants requires strategies to expand the donor pool. Successful use of hepatitis B virus (HBV)-positive grafts has been reported in liver transplantation. METHODS: In this United Network for Organ Sharing database (January 1999 to June 2021) retrospective cohort study, outcomes of kidney transplant (KT) or heart transplant (HT) recipients with HBV donor grafts (hepatitis B surface antigen and/or for HBV nucleic acid test-positive) were examined. Propensity score matching was performed for HBV-positive to negative graft recipients (1:5 for renal transplantation and 1:10 for HT). RESULTS: Of 448 HBV-positive donors with 896 kidneys, 352 kidneys (39.3%) and 56 hearts (12.5%) were transplanted. Of these, 312 kidneys (88.6%) and 45 hearts (80.3%) were transplanted in hepatitis B surface antigen-negative recipients. Ten-year graft survival was 47.1% and 49% (log-rank P = 0.353), and patient survival was 58% and 59% ( P = 0.999) for KT recipients. Similar figures among HT recipients were 41.9% and 38.9% for graft survival ( P = 0.471), and 54.3% and 61.2% for patient survival ( P = 0.277). Subgroup analyses in recipients with HBV nucleic acid test-positive grafts irrespective of antibodies to HBV core antigen-positive status, and recipients negative for anti-HBs (548 renal transplantation and 209 HT) were similar. CONCLUSIONS: Although we are limited by lack of available data on posttransplant anti-HBV treatment, the study observations suggest that using HBV-positive grafts is a reasonable strategy to expand the donor pool among candidates waiting for KT or HT.

Increased spine bone density in patients with chronic hepatitis B switched to tenofovir alafenamide: A prospective, multinational study.

BACKGROUND: Data on patients switched to tenofovir alafenamide (TAF) from nucleos(t)ide analogues (NUCs) other than tenofovir disoproxil fumarate are limited. AIMS: To assess the treatment and renal/bone safety outcomes following the switch to TAF. METHODS: We prospectively enrolled adult patients with chronic hepatitis B (CHB) who switched from any NUC to TAF at 14 centres in Japan, Korea, Taiwan and the U.S. Study outcomes were viral suppression (VR; HBV DNA < 20 IU/mL), biochemical response (BR; alanine aminotransferase normalisation), and changes in estimated glomerular filtration rate (eGFR) and T-scores (L-spine) by bone absorptiometry by 24 months after switch to TAF. RESULTS: We enrolled 270 eligible patients. Mean age was 58.1; 58.2% were male; 12.2% had cirrhosis and 73.3% previously received entecavir monotherapy. VR rate increased significantly from 95.2% to 98.8% by 24 months after the switch to TAF (p = 0.014). Between the switch and 24 months later, the mean spine T-score improved significantly from -1.43 ± 1.36 to -1.17 ± 1.38 (p < 0.0001), while there was no significant change in mean eGFR (88.4 ± 16.9-89.5 ± 16.3 mL/min/1.73 m2 , p = 0.13). On multivariable analysis adjusted for age, sex, baseline spine T-score and prior TDF or adefovir dipivoxil use, male sex was significantly associated with lower risk of worsening spine T-score (odds ratio: 0.29, p = 0.020), while age was significantly associated with a higher risk of worsening chronic kidney disease stage (OR: 1.07, p = 0.019). CONCLUSIONS: At 24 months after the switch to TAF, VR rates and spine bone density improved significantly while renal function remained stable.

Treatment rates and factors associated with direct-acting antiviral therapy for insured patients with hepatitis C-related hepatocellular carcinoma - A real-world nationwide study.

BACKGROUND: Since the inception of the interferon-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection, guidelines as to who should receive this potentially curative treatment have evolved. Treatment with DAAs is now considered for all patients except for those considered moribund. AIM: To determine the DAA treatment rate for patients with HCV-related hepatocellular carcinoma (HCC). METHODS: This was a retrospective study from January 2015 to March 2021 of a national sample of privately insured patients with HCV-related HCC using Optum's Clinformatics® Data Mart (CDM) Database - a large, de-identified, adjudicated claims database. RESULTS: We identified 3922 patients with HCV-related HCC: 922 (23.5%) received DAA. Compared to untreated patients, DAA-treated patients were younger (65.2 ± 7.5 vs. 66.4 ± 7.5 years, p < 0.001), more frequently saw a gastroenterology/infectious disease (GI/ID) physician (41.2% vs. 34.2%), and had decompensated cirrhosis (56% vs. 53%, p = 0.001). In multivariable analysis, younger age (HR: 0.98, 95% CI: 0.97-0.99, p < 0.001), GI/ID care (HR: 3.06, 95% CI: 2.13-4.51, p < 0.001), and having cirrhosis (compensated: HR: 1.60, 95% CI: 1.18-2.21, p = 0.003; decompensated: HR: 1.45, 95% CI: 1.07-1.98, p = 0.02) were associated with receiving DAA treatment, but not sex, race, or ethnicity. DAA-treated patients had significantly higher 5-year survival than untreated patients (47.2% vs. 35.2%, p < 0.001). Following adjustment for age, sex, race/ethnicity, Charlson Comorbidity Index, and HCC treatment, receiving DAA treatment was associated with lower mortality (aHR: 0.61, 95% CI: 0.53-0.69, p < 0.001). CONCLUSION: DAA treatment remains underutilised in insured patients with HCV-related HCC; fewer than one in four patients received treatment. Seeing a specialist and having decompensated cirrhosis were predictors for DAA treatment; additional efforts are needed to increase awareness of HCV treatment.